Age Related Macular Degeneration (ARMD) and Diabetic Retinopathy (DR) are the leading causes of visual loss in industrialized nations and do so as a result of abnormal retinal neovascularization. Since the retina consists of well-defined layers of neuronal, glial, and vascular elements, relatively small disturbances such as those seen in vascular proliferation or edema can lead to significant loss of visual function. Inherited retinal degenerations, such as Retinitis Pigmentosa (RP), are also associated with vascular abnormalities, such as arteriolar narrowing and vascular atrophy. While significant progress has been made in identifying factors that promote and inhibit angiogenesis, no treatment is currently available to specifically treat ocular vascular disease.
For many years it has been known that a population of stem cells exists in the normal adult circulation and bone marrow. Different sub-populations of these cells can differentiate along hematopoietic lineage positive (Lin+) or non-hematopoietic, lineage negative (Lin−) lineages. Furthermore, the lineage negative hematopoietic stem cell (HSC) population has recently been shown to contain endothelial progenitor cells (EPC) capable of forming blood vessels in vitro and in vivo. Asahara et al. Science 275, 964–7 (1997). These cells can participate in normal and pathological postnatal angiogenesis (See Lyden et al. Nat. Med. 7, 1194–201 (2001); Kalka et al. Proc. Natl. Acad. Sci. U.S.A. 97, 3422–7 (2000); and Kocher et al. Nat. Med. 7, 430–6 (2001)) as well as differentiate into a variety of non-endothelial cell types including hepatocytes (See Lagasse et al. Nat. Med. 6, 1229–34 (2000)), microglia (See Priller et al. Nat. Med. 7, 1356–61 (2002)), cardiomyocytes (See Orlic et al. Proc. Natl. Acad. Sci. U.S.A. 98, 10344–9 (2001)) and epithelium (See Lyden et al. Nat. Med. 7, 1194–201 (2001)). Although these cells have been used in several experimental models of angiogenesis, the mechanism of EPC targeting to neovasculature is not known and no strategy has been identified that will effectively increase the number of cells that contribute to a particular vasculature.